18F-FDG PET–derived parameter total lesion glycolisis (TLG) as a tool to stratify patients (pts) with advanced non–small cell lung cancer (aNSCLC) treated with immunotherapy.
Authors: Filippo Gustavo Dall'Olio, Camilo Garcia, Valentina Ambrosini, Marco Tagliamento, Carole Helissey, Monica Velasco, Mohamed Aymen Bettayeb, Mihaela Aldea, Nicole Conci, Matteo Bauckneht, Gerald Bonardel, Giulia Argalia, Davide Soldato, Eugenia Cella, Jordi Remon Masip, David Planchard, Corinne Balleyguier, Andrea Ardizzoni, Fabrice Barlesi, Benjamin Besse
Journal: Journal of Clinical Oncology (2022)

9062 Background: Upfront Immune Checkpoint Blockers (ICB) alone or in combination with chemotherapy (CT) have become the backbone treatment of non-oncogene addicted aNSCLC. PD-L1 remains the only predictive biomarker, but additional biomarkers are mandatory to better discriminate the population more suitable for the combination approach (CT-ICB). We hypothesized that TLG, a parameter that measure tumor burden and metabolic activity, may help to select the optimal first-line regimen. Methods: We performed a multicentric (n = 5) retrospective study including pts treated either with ICB alone, CT-ICB or CT alone. Overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier analysis. Hazard ratios (HR) were calculated using multivariate Cox proportional Hazard models adjusting for relevant covariates (neutrophil/lymphocyte ratio, ECOG PS, liver, bone metastases). TLG was calculated on PET scans as the product of metabolic tumor volume (with a threshold of 42% of SUV max) and SUV mean. Results: 250 pts with aNSCLC initiated first-line treatment (94 ICB, 102 CT-ICB and an hystorical control group of 54 CT) within 42 days from PET. Median follow up was 22 months for ICB, 16 for CT-ICB and 47 for CT. 170 pts were male (68%), 210 had non-squamous histology (84%), 110 (44%)and 38 (15%) had bone and liver metastasis, respectively. On the 194 pts with PD-L1 status available: 20%, 29% and 50% had PD-L1 &lt; 1%, 1-49% and &gt; 50%, respectively. No correlation was seen between PD-L1 and TLG. Presence of liver metastases (13% vs 2%) and ECOG PS &gt; 1 (16% vs 3%) were associated with elevated TLG. PFS correlated with TLG, with longer median PFS in the lower quartile (TLG &lt; 380) either with ICB (12.4 vs 4.7 months, HR 1.9, 95% CI1.1 – 3.35, p 0.025) and CT-ICB (17.9 vs 7.3, HR 1.9, 95% CI1.1 – 3.7, p 0.032) but not with CT (4.2 vs 3.5, p 0.986), whereas OS was correlated with TLG &lt; 380 in all 3 groups. The risk of progression under ICB was lower in tumors with TLG &lt; 380 (15% vs.29%, p = 0.02), but no difference was seen in other 2 groups. In PD-L1 ≥50% pts with elevated TLG, treatment with CT-ICB (n = 20) increased the PFS respect with ICB (n = 55) (10.7 vs 3.9, HR 0.54, 95% CI 0.29 – 0.99, p = 0.048).The analysis was underpowered to find a difference in OS (HR 0.49, 95% CI 0.21 - 1.12, p = 0.092). Conclusions: TLG retains a prognostic validity in aNSCLC identifying pts with an increased rate of early progression on ICB, who may benefit from CT-ICB. Further analyses are required to compare CT-ICB and ICB in PD-L1 ≥50% according to TLG. Enrollement from other centers is ongoing, an update will be presented.